Ceramic encapsulation by use of one or more specialized silanes to template oil in an oil in water emulsion

ABSTRACT

This invention relates to a method for emulsion templating hollow silica-based particles. The particles are suitable for containing one or more active ingredients or for containing other smaller particles which may include one or more active ingredients. The emulsion templated particles can be formed from two or more silanes. The emulsion templated particles can also be formed from a silane and a compound that attaches a polymer on the shell of the hollow silica-based particles.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation that claims the benefit of priorityand filing date pursuant to 35 U.S.C. § 120 to U.S. patent applicationSer. No. 13/011,564, filed Jan. 21, 2011, a U.S. Non-Provisional patentapplication that claims priority to U.S. Provisional Patent ApplicationSer. No. 61/297,122, filed Jan. 21, 2010.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

Not Applicable.

BACKGROUND OF THE INVENTION 1. Field of the Invention

This invention relates to a method for forming hollow silica-basedparticles suitable for containing one or more active ingredients or forcontaining other smaller particles which can include one or more activeingredients.

2. Description of the Related Art

One approach to providing an active ingredient to a surface, such as theskin, is to encapsulate the active ingredient in order to protect theactive ingredient, control the release of the active ingredient, and/ormodify the function of the active ingredient. Methods for encapsulationof an active ingredient, such as sol-gel encapsulation, are known in theart. See, for example U.S. Patent Application Publication No.2008/0317795 to Traynor et al.

Even with the advances in the art described in U.S. 2008/0317795, thereis still a need for further improved encapsulation techniques.

SUMMARY OF THE INVENTION

The present invention provides an oil in water emulsion for formingsilica-based particles that encapsulate one or more active ingredientsor encapsulate other smaller particles which can include one or moreactive ingredients. The oil in water emulsion includes an aqueouscontinuous phase; a dispersed phase comprising droplets including anon-polar material and/or one or more oils; and two different silicaprecursors, wherein the silica precursors can be templated on thedroplets to form the silica-based particles. The present invention alsoprovides a templated silica particle formed from the oil in wateremulsion of the invention wherein the silica particle can be modifiedfrom a continuously formed shell to a partially formed hollow shell byadjusting a ratio of the two silica precursors in the emulsion.

The present invention also provides an oil in water emulsion for makingsilica-based particles. The emulsion includes an aqueous continuousphase; a dispersed phase comprising droplets including a non-polarmaterial; and an organically modified silica precursor with at least onecarbon, wherein the silica precursor can be templated on the droplets tomake the silica-based particles.

The present invention also provides an oil-in-water emulsion system formaking silica coated particles. The emulsion includes an aqueouscontinuous phase; a surfactant component comprising a surfactantselected from anionic surfactants, nonionic surfactants, cationicsurfactants, nonionic surfactants, and mixtures thereof, each surfactantin the surfactant component being at or below a critical micelleconcentration of each surfactant; a dispersed phase comprising one ormore non-polar materials that are incompatible with the aqueous phaseand form droplets; a first organically modified silica precursor havinga carbon atom and having a first functional group that is capable offurther reaction, and a second organically modified silica precursorhaving a carbon atom that is combined with the first organicallymodified silica precursor and having a second functional group, whereinthe carbon atom of the second precursor and the second functional groupare in a ratio from 1 to 99 to 99 to 1, and wherein the firstorganically modified silica precursor and the second organicallymodified silica precursor can be reacted to form precipitated silicashells around the droplets which act as templates.

The present invention also provides a method for forming hollowsilica-based particles. The method includes (a) preparing an emulsionincluding a continuous phase that is polar, and a dispersed phasecomprising droplets including a non-polar active ingredient; (b) addinga first silica precursor to the emulsion such that the first silicaprecursor is emulsion templated on the droplets to form hollowsilica-based particles having a shell and a core including the non-polaractive ingredient, wherein the first silica precursor has the generalformula (I):R¹ _(x)—Si—(OR²)_(y)  (I)wherein R¹ is selected from substituted and unsubstituted alkyl, aryl,alcohols, amines, amides, aldehydes, acids, esters, and functionalgroups having an unsaturated carbon-carbon bond, wherein R² is an alkylgroup, wherein x+y=4, and wherein x=0 or 1 or 2; and (c) adding a secondprecursor to the emulsion such that a coating can be deposited on atleast part of the shell of the hollow silica-based particles.

In one example embodiment, the invention provides a method for forminghollow silica-based particles. In this method, an emulsion is preparedthat includes a continuous phase that is polar, and a dispersed phasecomprising droplets including a non-polar active ingredient. A firstsilica precursor is added to the emulsion such that the first silicaprecursor is emulsion templated on the droplets to form hollowsilica-based particles having a shell and a core including the non-polaractive ingredient. In one form, the first silica precursor has thegeneral formula (I):R¹ _(x)—Si—(OR²)_(y)  (I)wherein R¹ is selected from substituted and unsubstituted alkyl, aryl,alcohols, amines, amides, aldehydes, acids, esters, and functionalgroups having an unsaturated carbon-carbon bond, wherein R² is an alkylgroup, wherein x+y=4, and wherein x=0 or 1 or 2. A second silicaprecursor is added to the emulsion such that the second silica precursorcan be deposited on the shell of the hollow silica-based particles. Inone form, the second silica precursor has the general formula (II):R³ _(m)—Si—(OR⁴)_(n)  (II)wherein R³ is selected from substituted and unsubstituted alkyl, aryl,alcohols, amines, amides, aldehydes, acids, esters, and functionalgroups having an unsaturated carbon-carbon bond, and aminofunctionalgroups, wherein R⁴ is an alkyl group, wherein m+n=4, and wherein m=0, 1,or 2. Optionally, a third silica precursor can be added to the emulsionsuch that the third silica precursor can be emulsion templated on thedroplets or deposited on the hollow silica-based particles to formhollow silica-based particles. The third silica precursor has thegeneral formula (III):R⁵ _(a)—Si—(OR⁶)_(b)  (III)wherein R⁵ is selected from substituted and unsubstituted alkyl,substituted and unsubstituted aryl, functional groups having anunsaturated carbon-carbon bond, functional groups having a carboxylicacid group, polymers of alkylene oxide, and aminofunctional groups, R⁶is an alkyl group, a+b=4, and a=0, 1, 2 or 3. In this method, at leastone of R¹ and R³ is preferably selected from phenyl, C₁₂-C₂₄ alkyl,substituted or unsubstituted acrylic acid, alkylamine, alkylcarboxylate, and alkyl quaternary amine.

In another example embodiment, the invention provides a method forforming hollow silica-based particles. In the method, an emulsion isprepared that includes a continuous phase that is polar, and a dispersedphase comprising droplets including a non-polar active ingredient. Asilica precursor is added to the emulsion such that the silica precursoris emulsion templated on the droplets to form hollow silica-basedparticles having a shell and a core including the non-polar activeingredient. In one form, the silica precursor has the general formula(I):R¹ _(x)—Si—(OR²)_(y)  (I)wherein R¹ is selected from substituted and unsubstituted alkyl, aryl,alcohols, amines, amides, aldehydes, acids, esters, and functionalgroups having an unsaturated carbon-carbon bond, wherein R² is an alkylgroup, wherein x+y=4, and wherein x=0 or 1 or 2. A compound is added tothe emulsion such that a polymer is attached on the shell of the hollowsilica-based particles. The polymer may be charged. In one form, thecompound is an unsaturated compound, or a water soluble polymerizablecompound. In this method, R¹ is preferably selected from phenyl, C₁₂-C₂₄alkyl, substituted or unsubstituted acrylic acid, alkylamine, alkylcarboxylate, and alkyl quaternary amine.

It is an advantage of the invention to provide a method forencapsulation of an active ingredient in hollow silica-based particlesin which unencapsulated particles formed in the method are minimized.

It is another advantage of the invention to provide a method forencapsulation of an active ingredient in hollow silica-based particlesin which the particles do not need to be post-loaded with the activeingredient.

It is another advantage of the invention to provide a method forencapsulation of an active ingredient in hollow silica-based particlesin which the reaction time is minimized in relation to otherencapsulation methods.

It is another advantage of the invention to provide a method forencapsulation of an active ingredient in hollow silica-based particlesin which Stober (unencapsulated) particles are minimized.

It is another advantage of the invention to provide a method forencapsulation of an active ingredient in hollow silica-based particlesin which the resulting particles do not become brittle when dried.

It is another advantage of the invention to provide a method forencapsulation of an active ingredient in hollow silica-based particlesin which the particles have a surface functionality or a chargeablesurface for attachment of additional molecules.

These and other features, aspects, and advantages of the presentinvention will become better understood upon consideration of thefollowing detailed description, drawings and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a scanning electron microscope (SEM) image of silica-basedparticles formed using a method of the invention.

FIG. 2 is another SEM image of silica-based particles formed using amethod of the invention.

FIG. 3 is yet another SEM image of silica-based particles formed using amethod of the invention.

FIG. 4 is still another SEM image of silica-based particles formed usinga method of the invention.

FIG. 5 is yet another SEM image of silica-based particles formed using amethod of the invention.

FIG. 6 is still another SEM image of silica-based particles formed usinga method of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides a method of forming silica-based particlesincluding a non-polar active ingredient. In the method, a non-polaractive ingredient, a surfactant, and water are combined and agitated toform an oil-in-water emulsion wherein the non-polar active ingredientand any optional non-polar diluent comprise a dispersed phase in theaqueous continuous phase. Silica precursors are added to theoil-in-water emulsion and mixed. The silica precursors hydrolyze andsilica-based particles are formed which include the non-polar activeingredient. Two or more different silica precursors may be used. Afterthe silica precursors hydrolyze and silica-based particles are formed,the particles can be spherical and/or monodisperse.

One example version of the invention is an oil in water emulsion forforming silica-based particles. The emulsion includes an aqueouscontinuous phase; a dispersed phase comprising droplets including anon-polar material and/or one or more oils; and two different silicaprecursors, wherein the silica precursors can be templated on thedroplets to form the silica-based particles. The emulsified droplets caninitiate reaction of the silica precursors at interfaces between thedispersed droplets and the continuous phase.

The oil in water emulsion can include a surfactant selected fromcationic, anionic, nonionic and amphoteric surfactants. The surfactantcan be introduced to the emulsion below a critical micelle concentrationof the surfactant for precursor interface interaction. A secondsurfactant can be introduced to the emulsion below a critical micelleconcentration of the second surfactant for precursor interfaceinteraction. The second surfactant can be selected from cationic,anionic, nonionic and amphoteric surfactants. The surfactant can beintroduced to the emulsion above a critical micelle concentration of thesurfactant, and a second surfactant can be introduced to the emulsionbelow a critical micelle concentration of the second surfactant forprecursor interface interaction, wherein the second surfactant isselected from cationic, anionic, nonionic and amphoteric surfactants.The surfactant can be introduced to the emulsion above a criticalmicelle concentration of the surfactant, and a second surfactant can beintroduced to the emulsion above a critical micelle concentration of thesecond surfactant for precursor interface interaction, wherein thesecond surfactant is selected from cationic, anionic, nonionic andamphoteric surfactants. The surfactant can be added above a criticalmicelle concentration of the surfactant to stabilize the particles andthen diluted to reduce the level of surfactant to maintain the levelbelow the critical micelle concentration of the surfactant before theprecursors are added for precursor interaction.

Cationic surfactants may be especially beneficial when used in themethod of the invention. The condensation reaction occurs at basic pHand therefore, any hydrolyzed silica precursor is deprotonated andtherefore negative at basic pH. When a cationic surfactant is present atthe dispersed phase-continuous phase interface, this drives thedeprotonated hydrolyzed silica precursor to the interface therebyspeeding up the reaction time. In addition, any positive charges onfunctional groups of the hydrolyzed silica precursor can drive furtherdeprotonated hydrolyzed silica precursor to the interface therebyspeeding up the reaction time.

At least one of the precursors can have multiple functionality. At leastone of the precursors can have functional groups capable of preventingor limiting aggregation of the particles. At least one of the precursorscan include a functional group that allows for attachment of a polymeror other molecular complex to a surface of the formed particles bycovalent linking. At least one of the precursors can include afunctional group having a net charge to attract towards an oppositecharge of the surfactant at interfaces between the droplets and thecontinuous phase. The emulsion can have a charge associated with thesurfactant to help speed up the reaction at interfaces between thedroplets and the continuous phase by targeting and directing precursorformation at interfaces between the droplets and the continuous phase ina quicker fashion.

At least one of the silica precursors can include a functional grouphaving a charge ratio to limit polar and non-polar penetrations throughinterfaces between the droplets and the continuous phase to allow betterstabilization of the emulsion as well as assist in reactions. At leastone of the precursors can include a combination of functional groups,and at least two of the combination of functional groups are selectedfrom functional groups that allow for attachment of a polymer or othermolecular complex to a surface of the particles by covalent linking, orfunctional groups having a net charge to attract towards an oppositecharge of a surfactant at interfaces between the droplets and thecontinuous phase, and/or functional groups having a charge ratio tolimit polar and non-polar penetrations through interfaces between thedispersed droplets and the continuous phase to allow betterstabilization of the emulsion as well as assist in reactions.

A primary precursor of the two silica precursors can leave a first shellthickness of 1 nanometer to 500 nanometers, or 2 nanometer to 200nanometers, or 2 nanometer to 100 nanometers, for the particle when thesilica precursors are templated on a droplet. A secondary precursor ofthe two silica precursors can bond to the first shell to create an outerlayer such that the first shell and the outer layer together have athickness in the range of 1 nanometer to 1 micron.

The emulsion can include two or more oils which remain as a core of asilica particle shell after drying. At least one oil can remain in asilica particle shell after being washed.

Another example version of the invention is an emulsion templated silicaparticle formed from the oil in water emulsion. The silica particle canbe modified from a continuously formed shell to a partially formedhollow shell by adjusting a ratio of two silica precursors in theemulsion. The weight ratio or the volume ratio of the first silicaprecursor to the second silica precursor can be from 1:99 to 99:1, or1:50 to 50:1, or 1:25 to 25:1, or 1:5 to 15:1, or 1:1 to 10:1. If athird silica precursor is used, the second silica precursor and thethird silica precursor can be added in a ratio from 1:99 to 99:1, or1:50 to 50:1, or 1:25 to 25:1, or 1:5 to 15:1, or 1:1 to 10:1.Preferably, the silica precursors are different. The weight ratio or thevolume ratio of the first silica precursor to the active ingredient canbe from 1:99 to 99:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:5 to 15:1,or 1:10 to 10:1, or 1:100 to 5:1, or 1:10 to 5:1. The weight ratio orthe volume ratio of the second silica precursor to the active ingredientcan be from 1:99 to 99:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:5 to15:1, or 1:10 to 10:1, or 1:100 to 5:1, or 1:10 to 5:1. If a thirdsilica precursor is used, the second silica precursor and the thirdsilica precursor can be added in a ratio from 1:99 to 99:1, or 1:50 to50:1, or 1:25 to 25:1, or 1:5 to 15:1, or 1:1 to 10:1. The weight ratioor the volume ratio of the surfactant to the active ingredient can befrom 1:99 to 99:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:5 to 15:1, or1:10 to 10:1, or 1:100 to 5:1, or 1:10 to 1:1.

The templated silica particle may lose its internal core due to partialformation from a limited molar ratio of the two silica precursors. Thesilica particle may include a partially formed shell from aid ofprecursor hindrance. In one form, the silica particle allows for one ormore particles of smaller size either with a pore or continuous shell tobe present in the partially formed shell. The templated silica particlecan have functional groups capable of attaching a coating by covalentbonding, non-covalent bonding, ionic bonding, electrostatic attraction,or any other attachment mechanism which allows for coating proximitywithin sub-nanometer ranges to 500 microns. The coating can be apolymeric material.

The templated silica particle can have multiple layering effects whiletrapping an active material inside layers. The templated silica particlecan have 1 to 100 layers of silica deposited when the silica precursorsare templated on a droplet. The particle can burst upon friction andrelease a payload contained within the particle. The particle can remainintact within environments of pH ranges from 0.01-14. The templatedsilica particle can be chemically altered and open for diffusion of apayload contained within the particle.

The templated silica particle can be formed from more than twoprecursors making a shell with a thickness of 1 nanometer to 5 microns.The templated silica can have an overall size of 10 nanometers to 250microns. The templated silica particle can include an oil droplet havinga size of 1 nanometer to 200 microns, or 800 nanometers to 80 microns.Preferably, the templated silica particle maintains a template volume ofgreater than 0.01%. Preferably, the particle maintains a template volumeup to 100% loading. Preferably, the particle maintains greater than0.01% of a loaded material if the loaded material dissipates or leachesfrom the particle. The templated silica particle allows for completerelease of a payload material from the particle when the particle isintact or ruptured. In one form, the particle releases one layer of aloaded material at a time. In another form, the templated silicaparticle releases multiple layers of a loaded material at a time. Thetemplated silica particle can release a loaded material due to coatingdissociation. The particle can remain completely or partially intact dueto a coating on the particle.

In one form, the templated silica particle has a zeta potential rangingfrom −80 mV to 150 mV. The zeta potential can be measured on a Zetasizerinstrument from Malvern Instruments, Malvern, UK, or on a ZetaPlus orZetaPALS instrument from Brookhaven Instruments, Holtsville, N.Y. Insome embodiments, the templated silica particles have a zeta potentialof at least about 5, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 45, 50, 55,60, 65, 70, 80, 90 or 100 mV. In some embodiments, the templated silicaparticles have a zeta potential of no more than about 15, 20, 25, 30,35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100, or 150 mV. In someembodiments, the zeta potential is between 10 and 70 mV, between 20 and65 mV, between 25 and 65 mV, between 30 and 60 mV, between 30 and 100mV, between 40 and 80 mV, between 70 and 100 mV or between 40 and 55 mV.

The templated silica particle can include an oil with a mixture ofsolids, semi solids, or other liquids or gases. The templated silicaparticle formed from the oil in water emulsion can have water solubleconstituents mixed in an oil forming the emulsion for the templating.

Yet another example version of the invention is an oil in water emulsionfor making silica-based particles. The emulsion includes an aqueouscontinuous phase; a dispersed phase comprising droplets including anon-polar material; and an organically modified silica precursor with atleast one carbon, wherein the silica precursor can be templated on thedroplets to make the silica-based particles. The organically modifiedsilica precursor can include at least one carbon on two, three or allfour bonding sites of silicon in the organically modified silicaprecursor. The organically modified silica precursor can include two ormore of the same organically modified groups on bonding sites of thesilicon in the organically modified silica precursor.

Still another example version of the invention is an oil-in-wateremulsion system for making silica coated particles. The emulsionincludes an aqueous continuous phase; a surfactant component comprisinga surfactant selected from anionic surfactants, nonionic surfactants,cationic surfactants, nonionic surfactants, and mixtures thereof, eachsurfactant in the surfactant component being at or below a criticalmicelle concentration of each surfactant; a dispersed phase comprisingone or more non-polar materials that are incompatible with the aqueousphase and form droplets; a first organically modified silica precursorhaving at least one carbon atom and having a first functional group thatis capable of further reaction, and a second organically modified silicaprecursor having at least one carbon atom that is combined with thefirst organically modified silica precursor and having a secondfunctional group, wherein the at least one carbon atom and the secondfunctional group are in a ratio from 1 to 99 to 99 to 1, wherein thefirst organically modified silica precursor and the second organicallymodified silica precursor can be reacted to form precipitated silicashells around the droplets which act as templates. The first functionalgroup can be selected from alcohols, amines, aldehydes, acids, esters,and groups including an unsaturated bond. The second functional groupcan be selected from alcohols, amines, aldehydes, acids, esters, andgroups including an unsaturated bond. The aqueous phase can include acompound to control viscosity, wherein the compound is selected fromwater soluble polymers, salts, alcohols, glycols, alkylene ethoxylates,and mixtures thereof. The dispersed phase can include a compound tocontrol viscosity, wherein the compound selected from oil solublepolymers, waxes, fatty alcohols, triglycerides, fatty acids, fattyamines, esters, hydrocarbons, and mixtures thereof.

A silica shell formed from this oil-in-water emulsion system can includean alcohol functional group on a surface of the silica shell that can befurther reacted with: (i) an acid, an acid anhydride or an acid chlorideto form an ester, or (ii) a hydrosilane that reacts to form a siloxygroup that will link alkyl siloxane compounds to the shell surface, or(iii) a chlorosilane that reacts to form a siloxy group that will linkalkyl siloxane compounds to the shell surface, or (iv) an epoxide thatwill react to form an ether group that will link alkyl groups (with orwithout additional functional groups) to the silica shell surface.

A silica shell formed from this oil-in-water emulsion system can includean amine functional group on a surface of the silica shell that can befurther reacted with: (i) an acid, an acid anhydride or an acid chlorideto form an amide, or (ii) an alkylhalide (or dimethyl sulfate or diethylsulfate) to form a 2º, 3º amine or a quaternary ammonium salt that willlink an alkyl group(s) (with or without additional functional groups) tothe silica sphere surface, or (iii) an amine salt with an epoxide thatwill react to form a 2º, 3º ammonium salt or a quaternary ammonium saltgroup that will link alkyl group(s) (with or without additionalfunctional groups) to the silica shell surface, or (iv) an aldehyde or aketone that will react to form an imine or Schiff base compounds thatwill link alkyl groups (with or without additional functional groups) tothe silica shell surface, or (v) an acid to form an ammonium salt on thesilica sphere surface to impart a positive (cationic) charge to thesilica sphere surface.

A silica shell formed from this oil-in-water emulsion system can includean aldehyde functional group on a surface of the silica shell that canbe further reacted with: (i) an aldehyde, ketone or ester to form analdol condensation product that will link alkyl groups (with or withoutadditional functional groups) to the silica shell surface, or (ii) anamine to form an imine or Schiff base compounds that will link alkylgroups (with or without additional functional groups) to the silicashell surface.

A silica shell formed from this oil-in-water emulsion system can includean acid functional group on a surface of the silica shell that can befurther reacted with: (i) an alcohol to form an ester that will linkalkyl groups (with or without additional functional groups) to thesilica shell surface, or (ii) an amine to form an amide that will linkalkyl groups (with or without additional functional groups) to thesilica shell surface, or (iii) an amine to form an ionic ammonium saltthat will link alkyl groups (with or without additional functionalgroups) to the silica shell surface, or (iv) a base to form an ionizedacid group that will impart a negative (anionic) charge to the silicasphere surface.

A silica shell formed from this oil-in-water emulsion system can includean ester functional group on a surface of the silica shell that can befurther reacted with: (i) an alcohol (or acid) group as required totransesterify to form a new ester linkage that will join alkyl groups(with or without additional functional groups) to the silica shellsurface, or (ii) an amine to form an amide that will link alkyl groups(with or without additional functional groups) to the silica shellsurface.

A silica shell formed from this oil-in-water emulsion system can includean unsaturated functional group on a surface of the silica shell thatcan be further reacted with: (i) a hydrosilane that reacts to form analkylsilane linkage that will join alkyl siloxane compounds to the shellsurface, or (ii) an additional unsaturated compound (along withappropriate catalysts or reaction conditions) to polymerize therebyattaching a polymer (that may have additional functional groups) to thesilica shell surface.

A silica shell formed from this oil-in-water emulsion system can includea polymer attached to the first functional group and/or the secondfunctional group on a surface of the silica. Preferred polymers includepolymers having one or more quaternary ammonium cations.

In one non-limiting example of the invention, an emulsion is formed byhomogenizing a mixture of oil (e.g., fragrance as an active ingredient)and a surfactant solution using a homogenizer. This process usually runsfrom 10-60 minutes. Then an oil in water emulsion is formed with thedesired oil droplet sizes. A certain volume of this emulsion istransferred to a reaction container for the emulsion templatingreaction. Ammonium hydroxide is first added to the emulsion solution asa basic catalyst for the sol-gel reaction with stirring. A pH of 8-12,and preferably 9-11 is used. Then a first silica precursor is introducedfor the preliminary silica shell formation around the surfactantstabilized oil droplets and the reaction solution is stirred for a timeperiod of anywhere between 2-24 hours. After this step, a second silicaprecursor is introduced over 30-60 minutes under stirring for thethickening of the shell and then after some time the stirring is stoppedand the reaction solution is allowed to sit for up to 2 days dependingon what shell thickness is desired for the hollow silica-basedparticles. Alternatively, the time periods for addition of the firstsilica precursor and the second silica precursor can overlap.Preferably, the first silica precursor and the second silica precursorare different. The silica particles formed can be modified fromcontinuously formed hollow shells to partially formed hollow shells byadjusting a ratio of the two silica precursors in the emulsion.

After the reaction is completed, a small volume of the reaction solutionis transferred into a vial for washing with water using a centrifuge forabout 3 times. At the end of washing, this solution is used to preparescanning electron microscope samples for investigation of the shellformation and size distribution. A vacuum filter with the appropriatemembrane pore size are used to collect the silica-based shells dry forlong term storage.

In the invention, a unique emulsion system is formed in the aqueousphase that stabilizes the emulsion, preventing the coalescence of theoil droplets while the organic silica precursor is reacting.

Active ingredients can be encapsulated within the hollow silica-basedparticles of the invention. The particles can be viewed as having twoparts, the core and the shell. The core contains the active ingredient,while the shell surrounds and protects the core. The core materials usedin the invention can be solid or liquid, and if liquid, can be, forexample, in the form of a pure compound, solution, dispersion oremulsion. The shell material can be a silica-based shell. The shell canbe made permeable, semi-permeable or impermeable. Permeable andsemi-permeable shells can be used for release applications. A permeableshell can be a shell including one or more passageways that extend froman inner surface of the shell (which is around the core) and the outersurface of the shell. Semi-permeable shells can be made to beimpermeable to the core material but permeable to low molecular-weightliquids and can be used to absorb substances from the environment and torelease them again when brought into another medium. The impermeableshell encloses the core material. To release the content of the corematerial, the shell must be ruptured.

The ceramic shells are prepared by a sol-gel based process in which asilica precursor is used. There are many silica precursors which canused in the present invention. For example, the silica precursor can bea silicate (silicon acetate, silicic acid or salts thereof), asilsequioxanes or poly-silsequioxanes, silicon alkoxides (e.g. fromsilicon methoxide to silicon octadecyloxide), and functionalizedalkoxides (such as ethyltrimethoxysilane, aminopropyltriethoxysilane,vinyltrimethoxysilane, diethyldiethoxysilane, diphenyldiethoxysilane,etc). Further specific examples of silica precursors includetetramethoxysilane (TMOS), tetraethoxysilane (TEOS), tetrabutoxysilane(TBOS), tetrapropoxysilane (TPOS), polydiethoxysilane,methyltrimethoxysilane, methyltriethoxysilane, ethyltriethoxysilane,phenyltriethoxysilane, octylpolysilsesquioxane andhexylpolysilsesquioxane. The silica precursor may include, for example,from one to four alkoxide groups each having from 1 or more oxygenatoms, and from 1 to 18 carbon atoms, more typically from 1 to 5 carbonatoms. The alkoxide groups may be replaced by one or more suitablefunctional groups. Examples of functional groups attached to silicaprecursors include alkyls, alcohols, amines (including quaternaryamines), amides, aldehydes, acids, esters, and groups including anunsaturated bond. Thus, an organically modified silica precursor can beused. An organically modified silica precursor can be a silica precursorwherein one or two (out of four) of the alkoxysilane groups has beenreplaced by organic groups like alkyls, alcohols, amines, amides,aldehydes, acids, esters, and groups including an unsaturated bond. Thesilica precursor may be a polysiloxane having, for example, 2 to 100repeat units and having one or more quaternary ammonium cations. Theprocessing is based on the hydrolysis and condensation of the silicaprecursors. Water is thus typically used as the condensing agent.

Various surfactants can be used in the method of the invention. In orderto form an oil-in-water emulsion of the invention, surfactants with anHLB value above about 8 are generally used. In some cases, multiplesurfactants are used. Where there are multiple surfactants, the combinedHLB of the surfactants is generally used. The HLB of the surfactant orsurfactants is between, for example, 7 and 13, 8 and 12, 9 and 11, 9.5and 10.5. In some embodiments, the HLB of the surfactants is 8, 8.5, 9,9.5, 10, 10.5, 11, 11.5, or 12. Surfactants suitable for forming theoil-in-water emulsion include anionic, non-ionic, cationic, andzwitterionic surfactants. Non-limiting example surfactants include:anionic—sodium oleate, sodium dodecyl sulfate, sodium diethylhexylsulfosuccinate, sodium dimethylhexyl sulfosuccinate, sodiumdi-2-ethylacetate, sodium 2-ethylhexyl sulfate, sodiumundecane-3-sulfate, sodium ethylphenylundecanoate, carboxylate soaps;cationic—dimethylammonium and trimethylammonium surfactants of chainlength from 8 to 20 and with chloride, bromide or sulfate counterion,myristyl-gammapicolinium chloride and relatives with alkyl chain lengthsfrom 8 to 18, benzalkonium benzoate, double-tailed quaternary ammoniumsurfactants with chain lengths between 8 and 18 carbons and bromide,chloride or sulfate counterions; nonionic: surfactants of the formC.sub.n(EO).sub.m where the alkane chain (C) length n is from 6 to 20carbons and the average number of ethylene oxide (EO) groups m is from 2to 80, ethoxylated cholesterol; zwitterionics andsemipolars—N,N,N-trimethylaminodecanoimide, amine oxide surfactants withalkyl chain length from 8 to 18 carbons,dodecyldimethylammoniopropane-1-sulfate, dodecyldimethylammoniobutyrate,dodecyltrimethylene diammonium chloride), decylmethylsulfonediimine,dimethyleicosylammoniohexanoate and relatives of these zwitterionics andsemipolars with alkyl chain lengths from 8 to 20.

Various non-polar active ingredients can be used in the inventiondepending on the final use for the silica-based particles. Non-limitingexamples for the active ingredient include sunscreens, steroidalanti-inflammatory actives, analgesic actives, antifungals,antibacterials, antiparasitics, anti-virals, anti-allergenics,anti-cellulite additives, medicinal actives, skin rash, skin disease anddermatitis medications, insect repellant actives, antioxidants, hairgrowth promoter, hair growth inhibitor, hair bleaching agents, deodorantcompounds, sunless tanning actives, skin lightening actives, anti-acneactives, anti-skin wrinkling actives, anti-skin aging actives, vitamins,nonsteroidal anti-inflammatory actives, anesthetic actives,anti-pruritic actives, anti-microbial actives, dental care agents,personal care agents, nutraceuticals, pharmaceuticals, fragrances,flavorings, antifouling agents, pesticides, lubricants, etchants, andmixtures and combinations thereof. In one example embodiment, thenon-polar active ingredient is a fragrance. In another exampleembodiment, the non-polar active ingredient is a sunscreen.

The size of the silica-based particles formed is determined, at least inpart, by the conditions of the reaction including the size of theoriginal emulsion, and the conditions used for formation of thesilica-based particles. A distribution of particle sizes can beobtained, or particles of a uniform size can be formed. The silica-basedparticles can also be fractionated into a desired size range afterformation. Fractionation can be carried out by methods known in the artsuch as selective precipitation, or by using filters or sieves in orderto pass a selected size range and retain the rest. The size of thesilica-based particles can be modified in order to suit a particularapplication.

In some embodiments, the mean size of the silica-based particles isbetween 10 nanometers and 1 millimeter, between 10 nanometers and 1 μm,between 1 μm and 100 μm, between 10 μm and 50 μm, between 50 μm and 200μm, or between 200 μm and 500 μm. In some embodiments, the mean size ofthe silica-based particles is between 1 nanometer and 10 nanometers,between 10 nanometers and 100 nanometers, between 100 nanometers and 1μm, between 150 nanometers and 800 nanometers, between 1 μm and 5 μm,between 1 μm and 10 μm, between 5 μm and 10 μm, between 1 μm and 20 μm,between 10 μm and 20 μm, between 10 μm and 100 μm, between 100 μm and 1millimeter, between 1 millimeter to 10 millimeters, or larger. In someembodiments, the mean size of the silica-based particles is within plusor minus 10% of 1 nanometer, 10 nanometers, 25 nanometers, 50nanometers, 75 nanometers, 90 nanometers, 100 nanometers, 250nanometers, 500 nanometers, 750 nanometers, 900 nanometers, 1 μm, 5 μm,10 μm, 25 μm, 50 μm, 75 μm, 90 μm, 100 μm, 250 μm, 500 μm, 750 μm, 900μm, 1 millimeter, or larger. In some embodiments, the mean size of thesilica-based particles is within plus or minus 50% of 1 nanometer, 10nanometers, 25 nanometers, 50 nanometers, 75 nanometers, 90 nanometers,100 nanometers, 250 nanometers, 500 nanometers, 750 nanometers, 900nanometers, 1 μm, 5 μm, 10 μm, 25 μm, 50 μm, 75 μm, 90 μm, 100 μm, 250μm, 500 μm, 750 μm, 900 μm, 1 millimeter, or larger. In someembodiments, the silica-based particles are monodisperse.

Thus, the method uses multifunctional silanes for particleencapsulation. The silanes can include functional groups such as: (1)lipophilic: aryls (e.g., phenyl); alkyls (e.g., behenyl, octyl, dodecyl,cetyl, stearyl, C₁₂-C₂₄ alkyl); (2) vinyl (e.g., acrylic acid); and (3)hydrophilic (e.g., polyethylene glycol, long chain alkylamine,carboxylates). The hollow shell layering can be controlled by thefunctional groups (such as phenyl and amine) that can block theencapsulation reaction, i.e., the thickness is varied by blocking groupsthat stop the reaction. Also, functional groups (such as phenyl) canalign at the continuous phase/dispersed phase interface and form pores,i.e., the porosity is controlled by the functionalized silanes. Inaddition, varying ratios of secondary silanes can stop the encapsulationreaction (to form thinner walls), or make the particles cationic, ormake the particles hydrophobic, and can control thicknesses of the wallsof the particles (e.g., 2-60 nm). Three secondary silanes can also bebeneficial (e.g., two cationics for net charge −0-80 mV zeta) forcontrolling reaction, or making cationic, or making hydrophobic.

The invention is further illustrated in the following Examples which arepresented for purposes of illustration and not of limitation.

EXAMPLES Example 1

An emulsion was formed by homogenizing a mixture of 5% of oil fragranceand 0.2% of a surfactant solution of Triton™ X-100 non-ionic surfactant(Octylphenol Ethoxylate, R—C₆H₄—O—(CH₂CH₂O)_(x)—H where R=octyl (C₈) andx=9.5 avg.) using a Polytron 3100 homogenizer. This process ran for 30minutes. An oil in water emulsion was formed with the desired oildroplet sizes. A volume of 25 milliliters of this emulsion wastransferred to a reaction container for an emulsion templating reaction.Ammonium hydroxide was first added at 2% to the emulsion solution ascatalyst for the sol-gel reaction with stirring, then 1 milliliter of afirst silica precursor, phenyltriethoxysilane, was introduced for thepreliminary silica shell formation around the surfactant stabilized oildroplets and the reaction solution was stirred for a time period of 2hours. After this step, 0.125 milliliters of a second silica precursor,tetramethoxysilane (TMOS), was introduced over 30 minutes under stirringfor the thickening of the shell and then after some time the stirringwas stopped and the reaction solution was allowed to sit for 1-2 daysfor the hollow silica-based particles. After the reaction was complete,a small volume of the reaction solution was transferred into a vial forwashing with water using a centrifuge for three times. At the end ofwashing, this solution was used to prepare scanning electron microscopesamples for investigation of the shell formation and size distribution.

FIG. 1 shows a first SEM image of silica-based particles formed usingthe emulsion templating reaction of the invention. Note in FIG. 1 howthe dual precursor, oil in water emulsion of the invention producedsilica-based particles in the range of 150-800 or 700-900 nanometers. Inthe SEM image of FIG. 1, the presence of hollow particles having acontinuously formed shell and hollow particles having a partially formedhollow shell can be seen. The formation of continuously formed shells orpartially formed hollow shell can be adjusted by the ratio of the twosilica precursors in the emulsion. Limited moles of silica precursor canprovide monopore shells as shown in FIG. 1. Furthermore, in the SEMimage of FIG. 1, the presence of a particle of smaller size within apore of a larger shell can be seen.

FIG. 2 shows a second SEM image of silica-based particles formed usingthis method of the invention. In the SEM image of FIG. 2, the presenceof a particle of smaller size within a pore of a larger shell can beseen. Without intending to be bound by theory, it is believed that thehydrophobic interior of the larger shell particle pulls the smallerparticle into the pore of the larger particle. Alternatively, particlesformed by the second silica precursor may form in the pore of the largerparticle.

FIG. 3 shows a third SEM image of silica-based particles formed usingthis method of the invention. In the SEM image of FIG. 3, the presenceof particles of uniform size can be seen. Uniform particles having asize above 1 micron are present.

FIG. 4 shows a fourth SEM image of silica-based particles formed usingthis method of the invention. In the SEM image of FIG. 4, the particlesare generally smooth. However, the small fuzziness on the particlesurfaces is believed to be an indicator of the functional groups of themodified silica precursor on the surface. Also, certain particles inFIG. 4 show binding at contact areas which is an indication of covalentlinking.

FIG. 5 shows a fifth SEM image of silica-based particles formed usingthe method of the invention. In the SEM image of FIG. 5, the presence ofspherical particles of a size below 100 nanometers can be seen. Also, ashell having a pore (i.e., a partially formed hollow shell) can be seen.

FIG. 6 shows a sixth SEM image of silica-based particles formed usingthis method of the invention wherein the aqueous phase included awater-soluble polymer (e.g., polymethylmethacrylate). The roughenedsurface shown in FIG. 6 indicates polymer build up and branching betweenthe vinyl functionalized surface of the shell of the particles. Thus,these particles have functional groups capable of attaching a coating bycovalent bonding, non-covalent bonding, ionic bonding, electrostaticattraction, or any other attachment mechanism.

Example 2

An emulsion was formed by homogenizing a mixture of 0.75 grams of oilfragrance and 23.85 milliliters of water and 0.04 grams of a surfactantsolution of Triton™ X-100 non-ionic surfactant (Octylphenol Ethoxylate,R—C₆H₄—O—(CH₂CH₂O)_(x)—H where R=octyl (C₈) and x=9.5 avg.) using aPolytron 3100 homogenizer. This process ran for 30 minutes. An oil inwater emulsion was formed with the desired oil droplet sizes. Ammoniumhydroxide was added at 1.25 milliliters to the emulsion solution asbasic catalyst for the sol-gel reaction with stirring, then 1.5milliliters of a first silica precursor, phenyltriethoxysilane, wasintroduced for the preliminary silica shell formation around thesurfactant stabilized oil droplets and the reaction solution was stirredfor a time period of 2 hours. After this step, 0.125 milliliters of asecond silica precursor, aminopropyltriethoxysilane, was introduced over30 minutes under stirring for the thickening of the shell and then aftersome time the stirring was stopped and the reaction solution was allowedto sit for 1-2 days for the hollow silica-based particles. After thereaction was complete, a small volume of the reaction solution wastransferred into a vial for washing with water using a centrifuge forthree times. At the end of washing, this solution was used to preparescanning electron microscope samples for investigation of the shellformation and size distribution. Very nice micron shells with minimalsmall ones were identified.

Example 3

An emulsion was formed by homogenizing a mixture of 0.5 grams of oilfragrance, 47.6 milliliters of water, 0.5 grams of a 10% solution ofMERQUAT 550 (an aqueous solution of a highly charged cationic copolymerof 30 mole % diallyl dimethyl ammonium chloride and 70 mole %acrylamide), and 0.4 grams of a 10% surfactant solution of Triton™ X-100non-ionic surfactant (Octylphenol Ethoxylate, R—C₆H₄—O—(CH₂CH₂O)_(x)—Hwhere R=octyl (C₈) and x=9.5 avg.) using a Polytron 3100 homogenizer.This process ran for 30 minutes. An oil in water emulsion was formedwith the desired oil droplet sizes. Ammonium hydroxide was added at 2.5milliliters to the emulsion solution as basic catalyst for the sol-gelreaction with stirring, then 2.5 milliliters of phenyltriethoxysilanewas introduced for the silica shell formation around the surfactantstabilized oil droplets and the reaction solution was stirred for a timeperiod of 2 hours. The stirring was stopped and the reaction solutionwas allowed to sit for 1-2 days for the hollow silica-based particles.After the reaction was complete, a small volume of the reaction solutionwas transferred into a vial for washing with water using a centrifugefor three times. At the end of washing, this solution was used toprepare scanning electron microscope samples for investigation of theshell formation and size distribution. Complete shells were identified.

Thus, the invention provides a method for forming hollow silica-basedparticles suitable for containing one or more active ingredients or forcontaining other smaller particles which may include one or more activeingredients.

Although the invention has been described in considerable detail withreference to certain embodiments, one skilled in the art will appreciatethat the present invention can be practiced by other than the describedembodiments, which have been presented for purposes of illustration andnot of limitation. Therefore, the scope of the appended claims shouldnot be limited to the description of the embodiments contained herein.

The invention claimed is:
 1. A method for forming silica-basedparticles, the method comprising the steps: (a) preparing an emulsionhaving a basic pH, the emulsion including a continuous phase that ispolar and has one or more nonionic surfactants and/or one or moreanionic surfactants, and a dispersed phase comprising droplets includinga non-polar active ingredient and a non-polar diluent; (b) adding afirst modified silica precursor to the emulsion such that the firstmodified silica precursor is emulsion templated onto the surface of thedroplets to form a silica-based first shell layer around the droplets,wherein the first shell layer formed has a mean thickness of about 1 nmto about 500 nm within 2 hours from addition of the first modifiedsilica precursor to the emulsion, and wherein the first modified silicaprecursor has the general formula (I):R¹ _(x)-Si-(OR²)_(y)  (I) wherein R¹ is selected from substituted andunsubstituted alkyl, aryl, alcohols, amines, amides, aldehydes, acids,esters, and functional groups having an unsaturated carbon-carbon bond,wherein R² is an alkyl group, wherein x+y=4, and wherein x=1 or 2; (c)adding a second modified silica precursor to the emulsion such that acoating can be deposited on at least part of the silica-based firstshell layer through the interaction of the second modified silicaprecursor with the first modified silica precursor present in thesilica-based first shell layer to form a second shell layer, wherein thefirst silica precursor and the second silica precursor are different;and (d) allowing the emulsion to sit for up to 2 days until thethickness of the first shell layer and the second shell layer togetherhave a mean thickness in the range of about 1 μm to about 250 μm;wherein the method produces silica-based particles having a silica-basedshell surrounding a liquid core comprising the non-polar activeingredient and the non-polar diluent.
 2. The method of claim 1, whereinthe second modified silica precursor has the general formula (II):R³ _(m)-Si-(OR⁴)_(n)  (II) wherein R³ is selected from substituted andunsubstituted alkyl, aryl, alcohols, amines, amides, aldehydes, acids,esters, and functional groups having an unsaturated carbon-carbon bond,and amino functional groups, wherein R⁴ is an alkyl group, whereinm+n=4, and wherein m=1 or
 2. 3. The method of claim 2, wherein at leastone of R¹ of the first modified silica precursor and R³ of the secondmodified silica precursor has a net charge to attract towards anopposite charge of a surfactant at interfaces between the droplets andthe continuous phase.
 4. The method of claim 2, wherein at least one ofR¹ of the first modified silica precursor and R³ of the second modifiedsilica precursor prevents or limits aggregation of the silica-basedparticles.
 5. The method of claim 2, wherein at least one of R¹ of thefirst modified silica precursor and R³ of the second modified silicaprecursor allows for attachment of a polymer or other molecular complexto a surface of the particles by covalent linking.
 6. The method ofclaim 2, wherein step (c) comprises adjusting a ratio of the firstmodified silica precursor and the second modified silica precursor tomodify the silica-based silica particle from a continuously formed shellto a partially formed shell.
 7. The method of claim 1, wherein theamount of the one or more nonionic surfactants and/or the one or moreanionic surfactants is below a critical micelle concentration of thesurfactant for precursor interface interaction.
 8. The method of claim1, wherein the amount of the one or more nonionic surfactants and/or theone or more anionic surfactants is above a critical micelleconcentration of the surfactant.
 9. The method of claim 1, wherein theone or more nonionic surfactants and/or the one or more anionicsurfactants speed up the reaction at interfaces between the droplets andthe continuous phase by targeting and directing precursor formation atinterfaces between the droplets and the continuous phase.
 10. The methodof claim 1, wherein the silica-based first shell layer has a first shelllayer thickness of about 2 nm to about 200 nm.
 11. The method of claim10, wherein the silica-based first shell layer has a first shell layerthickness of about 2 nm about 100 nm.
 12. The method of claim 1, whereinthe second precursor is a water soluble polymeric compound or anunsaturated compound, and the coating includes a polymer.
 13. The methodof claim 12, wherein the second precursor is a water soluble polymericcompound.
 14. The method of claim 12, wherein R¹ of the first modifiedsilica precursor allows for attachment of the water soluble polymericcompound or the unsaturated compound to a surface of the particles bycovalent linking.
 15. The method of claim 1, wherein the non-polaractive ingredient is an oil, and the method further comprises washingthe silica-based particles such that the oil remains in the shell of thesilica-based particles after being washed.
 16. The method of claim 1,wherein the silica-based particles have a Zeta potential range from 0 mVto 150 mV.
 17. The method of claim 1, wherein the liquid core comprisesthe hydrophobic active ingredient in the form of a solution, dispersion,or emulsion.
 18. The method of claim 1, wherein the shell is a mono-poreshell.
 19. The method of claim 1, wherein the non-polar activeingredient includes a sunscreen, a steroidal anti-inflammatory active,an analgesic, active, an antifungal, an antibacterial, an antiparasitic,an antiviral, an anti-allergenic, an anti-cellulite additive, amedicinal active, a skin rash medication, a skin disease medication, adermatitis medication, an insect repellant active, an antioxidant, ahair growth promoter, a hair growth inhibitor, a hair bleaching agent, adeodorant compound, a sunless tanning active, a skin lightening active,an antiacne active, an anti-skin wrinkling active, an anti-skin agingactive, a vitamin, a nonsteroidal anti-inflammatory active, ananesthetic active, an anti-pruritic active, an anti-microbial active, adental care agent, a personal care agent, a nutraceutical, apharmaceutical, a fragrance, a flavoring, a antifouling agent, apesticide, a lubricant, an etchant, mixtures thereof or combinationsthereof.